Flies "R" us: fruit fly cells mimic the mammalian pancreas.

Chalk up yet another surprise from the common fruit fly, Drosophila melanogaster, which serves as the quintessential model for investigating genetics and many diseases. A new study suggests that the tiny insects and people share even more biology than researchers had expected: The flies have cells that function much as those in the human pancreas do.

The pancreas appears in physiologically complex animals such as mammals and birds but not in insects. It contains two cell types that exert opposing effects. Beta cells secrete insulin, a hormone that prompts tissues to take in sugars and other nutrients, thereby lowering blood sugar concentrations. Conversely, alpha cells secrete glucagon, a hormone that triggers tissues to release sugar into the bloodstream. If functioning properly, both cell types sense blood-sugar concentration, then together keep it within a healthy range. Pancreas malfunction results in diseases such as diabetes.

In 2002, Eric Rulifson, then a postdoctoral fellow at Stanford University, and his colleagues found cells in the fruit fly brain that sense blood sugar and secrete insulin as pancreatic beta cells do. "It suggested that much of the biology of insulin had been passed down in animal evolution from a common ancestor 550 million years ago," says Rulifson. However, the researchers were missing the second half of the pancreatic equation: cells, like alpha cells, that sense blood sugar and secrete a hormone to offset insulin's effects.

Rulifson, currently at the University of Pennsylvania School of Medicine in Philadelphia, and Seung Kim, his collaborator at Stanford, have now discovered a likely candidate: corpora cardiaca (CC) cells, located near insulin-secreting cells in the Drosophila brain.

After the scientists used genetic modifications to kill CC cells in fly larvae, the larvae had low blood sugar concentrations. When the scientists then gave these larvae an activated copy of the gene for the hormone that CC cells make, the flies' blood sugar returned to normal. The findings, published in the Sept. 16 Nature, suggest that the CC-cell hormone plays a role similar to glucagon's.

However, in a variation from pancreatic function, healthy flies dosed with a diabetes medication that blocks sugar sensors secreted too much of the glucagonlike hormone and developed skyrocketing blood sugar concentrations. These results indicate that the sensors occur only on the flies' alphalike cells, although they appear on both alpha and beta cells in mammals.

Since the alphalike cells seem to hold primary control over blood sugar in Drosophila, a relatively primitive organism, Rulifson notes that they may be evolutionarily older than beta cells. "Maybe the alpha cell is the more ancestral cell type, and the beta cell is an adaptation of that cell," he says.

Roger Unger, a diabetes researcher at the University of Texas Southwestern Medical Center in Dallas,

praises the study but doubts that fruit flies will ever be in vogue for diabetes studies. "We have mammalian models that are much closer to humans" he says.

However, says Kim, Drosophila hold several advantages for scientists, such as their tiny size, rapid breeding, and low expense to maintain. Because the flies responded to an anti-diabetes medication, he suggests that they could eventually become attractive for screening new diabetes-fighting drugs.